PD‐L1 in squamous cell carcinoma of the oral tongue shows gender‐specific association with prognosis

Abstract

Objective To use alternative quantitation approaches to clarify the clinical implication of programmed cell death ligand 1 (PD‐L1) in squamous cell carcinoma of the oral tongue (SCCOT). Materials and Methods Ventana SP263 immunohistochemistry assay and a multiplicative QuickScore method were applied to quantify PD‐L1 in tumor and surrounding immune cells from 101 patients with SCCOT. Tumor‐infiltrating immune cells were estimated from bulk tissue transcriptional profiles of 25 patients. Circulating PD‐L1 levels were measured in serum from 30 patients using an electrochemiluminescence assay platform. Results We found higher tumor cell PD‐L1 levels in females than males (p = .019). For patients with low PD‐L1 in tumor cells, better survival was seen in males than females (overall survival p = .021, disease‐free survival p = .020). Tumor‐infiltrating natural killer T cells, immature dendritic cells, and M1 macrophages were positively associated with tumor cell PD‐L1 (p < .05). Conclusions Our data confirmed the significance of gender on tumor cell PD‐L1 expression and demonstrated combined effects of gender and PD‐L1 levels on clinical outcome in patients with SCCOT. The data also indicated the involvement of specific immune cell types in PD‐L1‐regulated immune evasion.

CXCL6 fuels the growth and metastases of esophageal squamous cell carcinoma cells both in vitro and in vivo through upregulation of PD‐L1 via activation of STAT3 pathway

“…Surprisingly, we have not observed a significant association of CXCL6 with overall prognosis in ESCC. Much like CXCL6, significant association has also failed to be reached between PD‐L1 expression and overall survival of patients with ESCC in our setting, which was inconsistent with a great deal of studies claiming that overexpressed PD‐L1 was markedly associated with shorter survival in tumors, regardless of their origins (Carlsson et al, 2020; Qian et al, 2020; Suzuki et al, 2020; Wilms et al, 2020). Fortunately, the observation we made concerning the prognostic prediction of PD‐L1 in ESCC was in step with one meta‐analysis performed in oral squamous cell carcinoma by Troiano et al (2019), concluding that PD‐L1 expression was unassociated with unfavorable prognoses.…”

The B7 family molecules in oral squamous cell carcinoma: a systematic review. Part I: B7-H1 (PD-L1) and B7-DC (PD-L2)

“…The occurrence of protein expression was as follows: PD-L1 – 18.4–100% and PD-L2 – 23.8–100%. PD-L1 protein was associated with gender [ 16 , 18 , 35 , 41 , 44 ], grading [ 19 , 48 ], primary tumour size (T stage) [ 21 , 29 , 30 ] and metastases in lymph nodes [ 17 , 25 , 39 , 48 ]. Staging was correlated with PD-L1 [ 17 , 20 , 30 ] and PD-L2 [ 33 ].…”

“…Only PD-L1 protein expression proved to be a prognostic factor. Overall survival [ 16 , 24 , 31 , 35 , 42 ], disease-free survival [ 16 , 20 , 45 ], progression-free survival [ 35 ], poor prognosis [ 26 ] and recurrence-free survival [ 42 ] were correlated with PD-L1 protein expression. Immunohistochemistry was the most commonly used diagnostic method.…”

High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments

“…In other works concerning OSCC, PD-L1 expression on TCs was observed with variable frequency ranging from approximately 10 to 90% of cases [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. The studies differed in the size of the study group, selection of patients, antibody clones used, and the way of assessing PD-L1 expression; the two latter factors in particular significantly influence the final results of the study.…”

“…Other research showed that high infiltration by CD4+ and CD8+ and high CD8+/FOXP3+ ratio lymphocytes were associated with positive expression of PD-L1 on TCs [ 33 ]. Other factors which influence PD-L1 expression in OSCC include gender, since some studies showed more PD-L1-negative tumors in males than in females [ 37 , 39 ]. Hanna et al [ 44 ] reported that PD-L1 expression was associated with better outcomes in young females with OSCC.…”